Abstract Among viruses that cause disease in humans the henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), stand out for their impressive lethality. These viruses are among the most deadly human pathogens known to man with case fatality rates averaging about 75% for NiV. Significantly, there is evidence of multiple rounds of person-to-person transmission of NiV. In addition to natural outbreaks of HeV in Australia and NiV primarily in India and Bangladesh, there is concern that HeV and NiV could be used as agents of bioterrorism. Currently, there are no henipavirus vaccines or treatments approved for human use. For these reasons Nipah and henipaviral diseases are one of only eight pathogens listed on the new World Health Organization R&D Blueprint list of epidemic threats needing urgent R&D action (http://www.who.int/blueprint/ priority- diseases/en/). All three of the Research Projects within the CETR focus on developing broad spectrum vaccines or therapeutics against HeV and NiV. RP1 employs a HeV soluble G (sG)-based vaccines that is currently licensed for horses in Australia. RP2 focuses on anti-henipavirus monoclonal antibodies, and RP3 focuses on attenuated henipavirus vaccines. A unique aspect of this CETR is that these approaches include the most promising vaccine (HeV sG) and the most promising antiviral (human monoclonal antibody m102.4) that have shown the ability to provide complete preventive and postexposure protection of nonhuman primates (NHPs) against henipaviruses, respectively. All three CETR Research Projects and Core B require that countermeasures be evaluated in animals. Federal law requires that HeV and NiV be handled in an approved Biosafety Level (BSL)-4 containment laboratory. Core C provides an approved BSL-4 facility and a trained and highly experienced team of BSL-4 investigators and staff to perform studies that support RP1-RP3 and Core B. Core C will perform ?well-documented? NHP efficacy studies and ?pivotal? NHP studies that will be conducted in accordance with a GLP-based quality agreement that will be supported by a dedicated quality assurance/quality control team. The services provided by Core C will include 1) a secure repository of well characterized seed stocks of BSL-4 henipaviruses 2) in vitro antiviral activity assays; 3) procurement of UTMB IACUC approval of animal protocols; 3) procurement, housing, and husbandry of animals; 5) virus challenge, treatment, and collection of samples from animals; 6) technical expertise and equipment to conduct clinical pathological and virological analysis of samples and to perform necropsies in BSL-4 containment; 7) histopathological analysis of tissues collected from animals infected with henipaviruses; and 8) quality systems management of all records and data collected from NHP studies. Relevance The BSL-4 Evaluation Core (Core C) provides BSL-4 resources and expertise for RP1, RP2, RP3, and Core B. The goal of Core C is to work closely with Research Project Leaders and staff, Scientific Advisory Committee, and NIAID/NIH to advance the development of countermeasures against HeV and NiV.